Kim, HyoYoung;Caetano-Anolles, Kelsey;Seo, Minseok;Kwon, Young-jun;Cho, Seoae;Seo, Kangseok;Kim, Heebal
Genomics & Informatics
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v.13
no.4
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pp.137-145
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2015
Selective sweep can cause genetic differentiation across populations, which allows for the identification of possible causative regions/genes underlying important traits. The pig has experienced a long history of allele frequency changes through artificial selection in the domestication process. We obtained an average of 329,482,871 sequence reads for 24 pigs from three pig breeds: Yorkshire (n = 5), Landrace (n = 13), and Duroc (n = 6). An average read depth of 11.7 was obtained using whole-genome resequencing on an Illumina HiSeq2000 platform. In this study, cross-population extended haplotype homozygosity and cross-population composite likelihood ratio tests were implemented to detect genes experiencing positive selection for the genome-wide resequencing data generated from three commercial pig breeds. In our results, 26, 7, and 14 genes from Yorkshire, Landrace, and Duroc, respectively were detected by two kinds of statistical tests. Significant evidence for positive selection was identified on genes ST6GALNAC2 and EPHX1 in Yorkshire, PARK2 in Landrace, and BMP6, SLA-DQA1, and PRKG1 in Duroc. These genes are reportedly relevant to lactation, reproduction, meat quality, and growth traits. To understand how these single nucleotide polymorphisms (SNPs) related positive selection affect protein function, we analyzed the effect of non-synonymous SNPs. Three SNPs (rs324509622, rs80931851, and rs80937718) in the SLA-DQA1 gene were significant in the enrichment tests, indicating strong evidence for positive selection in Duroc. Our analyses identified genes under positive selection for lactation, reproduction, and meat-quality and growth traits in Yorkshire, Landrace, and Duroc, respectively.
To clarify the role of long intergenic nonprotein-coding RNA 1232 (LINC01232) in the progression of gastric cancer and the potential mechanism, we analyzed the expression of LINC01232 in TCGA database using the GEPIA online tool, and the LINC01232 level in gastric cancer cell lines was detected by quantitative real time-polymerase chain reaction (qRT-PCR) as well. Cell proliferation assay, colony formation assay, transwell assay and tumor formation experiment in nude mice were conducted to observe the biological behavior changes of gastric cancer cells through the influence of LINC01232 knockdown. LncATLAS database and subcellular isolation assay were used for subcellular distribution of LINC01232 in gastric cancer cells. The interaction among LINC01232, zeste homolog 2 (EZH2) and kruppel-like factor 2 (KLF2) was clarified by RNA-protein interaction prediction (RPISeq), RNA immunoprecipitation (RIP), qRT-PCR and chromatin immunoprecipitation (ChIP) assay. Rescue experiments were further conducted to elucidate the biological function of LINC01232/KLF2 axis in the progression of gastric cancer. LINC01232 was upregulated in stomach adenocarcinoma (STAD) tissues and gastric cancer lines. LINC01232 knockdown inhibited the proliferative capacities of gastric cancer cells in vitro, and impaired in vivo tumorigenicity. LINC01232 was mainly distributed in the cell nucleus where it epigenetically repressed KLF2 expression via binding to the enhancer of EZH2, which was capable of binding to promoter regions of KLF2 to induce histone H3 lysine 27 trimethylation (H3K27me3). LINC01232 exerts oncogenic activities in gastric cancer via inhibition of KLF2, and therefore, the knockdown of KLF2 could reverse the regulatory effect of LINC01232 in the proliferative ability of gastric cancer cells.
Kim, Jinsoo;Shin, Woo-Ri;Kim, Yang-Hoon;Shim, Donghwan;Ryu, Hojin
Journal of Plant Biotechnology
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v.48
no.3
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pp.148-155
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2021
Gibberellins (GAs) are essential phytohormones for plant growth that influence developmental processes and crop yields. Recent functional genomic analyses of model plants have yielded good characterizations of the canonical GA signaling pathways and related genes. Although Panax ginseng has long been considered to have economic and medicinal importance, functional genomic studies of the GA signaling pathways in this crucial perennial herb plant have been rarely conducted. Here, we identified and performed functional analysis of the GA signaling-related genes, including PgGID1s, PgSLY1s, and PgRGAs. We confirmed that the physiological role of GA signaling components in P. ginseng was evolutionarily conserved. In addition, the important functional domains and amino acid residues for protein interactions among active GA, GID1, SCFSLY1, and RGA were also functionally conserved. Prediction and comparison of crystallographic structural similarities between PgGID1s and AtGID1a supported their function as GA receptors. Moreover, the subcellular localization and GA-dependent promotion of DELLA degradation in P. ginseng was similar to the canonical GA signaling pathways in other plants. Finally, we found that overexpression of PgRGA2 and PgSLY1-1 was sufficient to complement the GA-related phenotypes of atgid1a/c double- and rga quintuple-mutants, respectively. This critical information for these GA signaling genes has the potential to facilitate future genetic engineering and breeding of P. ginseng for increased crop yield and production of useful substances.
Gazi, Md. Amran;Mahmud, Sultan;Fahim, Shah Mohammad;Kibria, Mohammad Golam;Palit, Parag;Islam, Md. Rezaul;Rashid, Humaira;Das, Subhasish;Mahfuz, Mustafa;Ahmeed, Tahmeed
Genomics & Informatics
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v.16
no.4
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pp.26.1-26.12
/
2018
Shigella spp. constitutes some of the key pathogens responsible for the global burden of diarrhoeal disease. With over 164 million reported cases per annum, shigellosis accounts for 1.1 million deaths each year. Majority of these cases occur among the children of the developing nations and the emergence of multi-drug resistance Shigella strains in clinical isolates demands the development of better/new drugs against this pathogen. The genome of Shigella flexneri was extensively analyzed and found 4,362 proteins among which the functions of 674 proteins, termed as hypothetical proteins (HPs) had not been previously elucidated. Amino acid sequences of all these 674 HPs were studied and the functions of a total of 39 HPs have been assigned with high level of confidence. Here we have utilized a combination of the latest versions of databases to assign the precise function of HPs for which no experimental information is available. These HPs were found to belong to various classes of proteins such as enzymes, binding proteins, signal transducers, lipoprotein, transporters, virulence and other proteins. Evaluation of the performance of the various computational tools conducted using receiver operating characteristic curve analysis and a resoundingly high average accuracy of 93.6% were obtained. Our comprehensive analysis will help to gain greater understanding for the development of many novel potential therapeutic interventions to defeat Shigella infection.
In diagnosis of lung cancer, rapid distinction between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) tumors is very important. Serum markers, including lactate dehydrogenase (LDH), C-reactive protein (CRP), carcino-embryonic antigen (CEA), neurone specific enolase (NSE) and Cyfra21-1, are reported to reflect lung cancer characteristics. In this study classification of lung tumors was made based on biomarkers (measured in 120 NSCLC and 60 SCLC patients) by setting up optimal biomarker joint models with a powerful computerized tool - gene expression programming (GEP). GEP is a learning algorithm that combines the advantages of genetic programming (GP) and genetic algorithms (GA). It specifically focuses on relationships between variables in sets of data and then builds models to explain these relationships, and has been successfully used in formula finding and function mining. As a basis for defining a GEP environment for SCLC and NSCLC prediction, three explicit predictive models were constructed. CEA and NSE are requentlyused lung cancer markers in clinical trials, CRP, LDH and Cyfra21-1 have significant meaning in lung cancer, basis on CEA and NSE we set up three GEP models-GEP 1(CEA, NSE, Cyfra21-1), GEP2 (CEA, NSE, LDH), GEP3 (CEA, NSE, CRP). The best classification result of GEP gained when CEA, NSE and Cyfra21-1 were combined: 128 of 135 subjects in the training set and 40 of 45 subjects in the test set were classified correctly, the accuracy rate is 94.8% in training set; on collection of samples for testing, the accuracy rate is 88.9%. With GEP2, the accuracy was significantly decreased by 1.5% and 6.6% in training set and test set, in GEP3 was 0.82% and 4.45% respectively. Serum Cyfra21-1 is a useful and sensitive serum biomarker in discriminating between NSCLC and SCLC. GEP modeling is a promising and excellent tool in diagnosis of lung cancer.
Park, Jeong-Woong;Song, Ki-Duk;Kim, Nam Young;Choi, Jae-Young;Hong, Seul A;Oh, Jin Hyeog;Kim, Si Won;Lee, Jeong Hyo;Park, Tae Sub;Kim, Jin-Kyoo;Kim, Jong Geun;Cho, Byung-Wook
Asian-Australasian Journal of Animal Sciences
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v.30
no.10
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pp.1471-1477
/
2017
Objective: Since athletic performance is a most importance trait in horses, most research focused on physiological and physical studies of horse athletic abilities. In contrast, the molecular analysis as well as the regulatory pathway studies remain insufficient for evaluation and prediction of horse athletic abilities. In our previous study, we identified AXL receptor tyrosine kinase (AXL) gene which was expressed as alternative spliced isoforms in skeletal muscle during exercise. In the present study, we validated two AXL alternative splicing transcripts (named as AXLa for long form and AXLb for short form) in equine skeletal muscle to gain insight(s) into the role of each alternative transcript during exercise. Methods: We validated two isoforms of AXL transcripts in horse tissues by reverse transcriptase polymerase chain reaction (RT-PCR), and then cloned the transcripts to confirm the alternative locus and its sequences. Additionally, we examined the expression patterns of AXLa and AXLb transcripts in horse tissues by quantitative RT-PCR (qRT-PCR). Results: Both of AXLa and AXLb transcripts were expressed in horse skeletal muscle and the expression levels were significantly increased after exercise. The sequencing analysis showed that there was an alternative splicing event at exon 11 between AXLa and AXLb transcripts. 3-dimentional (3D) prediction of the alternative protein structures revealed that the structural distance of the connective region between fibronectin type 3 (FN3) and immunoglobin (Ig) domain was different between two alternative isoforms. Conclusion: It is assumed that the expression patterns of AXLa and AXLb transcripts would be involved in regulation of exercise-induced stress in horse muscle possibly through an $NF-{\kappa}B$ signaling pathway. Further study is necessary to uncover biological function(s) and significance of the alternative splicing isoforms in race horse skeletal muscle.
In this study, we aimed to identify the nonsynonymous single nucleotide polymorphisms (nsSNPs) located in lipid metabolism-related genes because lipids are an important factor affecting the taste and flavor of meat, and they predict the functional consequences. The results showed that we identified 139 common nsSNPs in all five Korean native chicken (KNC) lines from the 81 genes related to lipid metabolism. Furthermore, sorting intolerant from tolerant (SIFT) and polymorphism phenotyping v2 (Polyphen-2) analyses predicted that among the genes, 14 nsSNPs of nine genes might be deleterious. Protein domain prediction of the nine genes revealed that all deleterious nsSNPs identified in this study were located outside the functional domain. This observation suggests that the common deleterious nsSNPs might be dispensable and have a minor effect on the traits of the KNCs.
Chibby family member 2 (CBY2), also known as SPERT or NURIT, is a gene with Chibby-like super family domain, whose function is not well known. In this study, the quail CBY2 gene was cloned, its sequences were analyzed, and its role in the myogenesis of QM7 quail muscle cells was characterized. Quail CBY2 has 978 nucleotides, which are translated into 325 amino acids, and the amino acid sequences are highly similar to those of chicken CBY2. Avian CBY2 diverted from mammalian CBY2 during early evolutionary history. According to the protein domain prediction analysis, quail CBY2 has a Chibby-like superfamily domain consisting of 83 amino acids at the N-terminal of the protein, although compared to mammalian CBY2, many of the amino acids were different. CBY2 was highly expressed in the adipose tissue and moderately expressed in the liver, heart, and kidney, whereas rarely expressed in the muscle tissue in quail. To characterize the role of CBY2 in myogenesis, CBY2 was overexpressed in QM7 cells. The overexpression of CBY2 inhibited myotube formation as shown that the myotube area was approximately only 25% that of the control. Taken together, quail CBY2 has a Chibby-like superfamily domain and inhibits myogenesis. Further studies should focus on the identification of the inhibitory mechanism of CBY2 on myogenesis.
Objective: The aim of this study was to reveal the role and regulatory mechanism of miR-188-5p in the proliferation and differentiation of goat muscle satellite cells. Methods: Goat skeletal muscle satellite cells isolated in the pre-laboratory were used as the test material. First, the expression of miR-188-5p in goat muscle tissues at different developmental stages was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). In addition, miR-188-5p was transfected into goat skeletal muscle satellite cells by constructing mimics and inhibitors of miR-188-5p, respectively. The changes of differentiation marker gene expression were detected by qPCR method. Results: It was highly expressed in adult goat latissimus dorsi and leg muscles, goat fetal skeletal muscle, and at the differentiation stage of muscle satellite cells. Overexpression and interference of miR-188-5p showed that miR-188-5p inhibited the proliferation and promoted the differentiation of goat muscle satellite cells. Target gene prediction and dual luciferase assays showed that miR-188-5p could target the 3'untranslated region of the calcium/calmodulin dependent protein kinase II beta (CAMK2B) gene and inhibit luciferase activity. Further functional studies revealed that CAMK2B promoted the proliferation and inhibited the differentiation of goat muscle satellite cells, whereas si-CAMK2B restored the function of miR-188-5p inhibitor. Conclusion: These results suggest that miR-188-5p inhibits the proliferation and promotes the differentiation of goat muscle satellite cells by targeting CAMK2B. This study will provide a theoretical reference for future studies on the molecular mechanisms of skeletal muscle development in goats.
Sepsis is a physiological response to a source of infection that triggers mechanisms that compromise organ function, leading to death if not treated early. Biomarkers with high sensitivity, specificity, speed, and accuracy that could differentiate sepsis from non-infectious systemic inflammatory response syndrome (SIRS) could bring about a revolution in sepsis treatment. Given the limitations and time required for microbial verification of pathogens, the accurate diagnosis of infection before employing antibiotic therapy is important and clinically necessary. Procalcitonin (PCT), lactate, C-reactive protein (CRP), cytokines, and proadrenomedullin (ProADM) are the common biomarkers used for diagnosis. The procalcitonin (PCT)-guided antibiotic treatment in patients with acute respiratory infections effectively reduces antibiotic exposure and side effects while improving survival rates. The evidence regarding sepsis screening in hospitalized patients is limited. Clinicians, researchers, and healthcare decision-makers should consider these findings and limitations when implementing screening tools, future research, or policy on sepsis recognition in hospitalized patients. The use of biomarkers in pediatric sepsis is promising, although such use should always be correlated with clinical evaluation. Biomarkers may also improve the prediction of mortality, especially in the early phase of sepsis, when the levels of certain pro-inflammatory cytokines and proteins are elevated.
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